The purpose of this project is to synthesize analogues of presqualene pyrophosphate and farnesyl pyrophosphate and test them as inhibitors of squalene synthetase. Inhibition studies will be performed with enzymes purified by affinity chromatography utilizing covalently bound inhibitors to either porous glass beads or beaded Agarose as the solid support. Inhibition studies will also be carried out utilizing intact cells from either kidney, blood, or liver. In addition, we will determine the substrate specificity of squalene synthetase and the molecular structure of the products from enzymatic incubation of the synthetic analogues.